Human immunodeficiency virus (HIV) has been implicated as the primary cause of the degenerative disease of the immune system termed acquired immune deficiency syndrome (AIDS). Infection of the CD4+ subclass of T-lymphocytes with the HIV type-1 virus (HIV-1) leads to depletion of this essential lymphocyte subclass which inevitably leads to opportunistic infections, neurological disease, neoplastic growth and eventual death.
Infection with human immunodeficiency virus (HIV) is a chronic process with persistent, high rates of viral replication. The pathogenesis of HIV-1 infection is characterized by a variable but often prolonged asymptomic period following the acute viremic phase.
Assays, which have been developed to detect the infection of HIV and monitor the progression of HIV in the body include inter-alia counting the depletion of CD4+ cells to indicate the prognosis of AIDS. In addition, serological screening techniques are also being utilized worldwide for the detection of HIV, where the presence of the antibody against HIV antigens, such as the HIV p24 antigen, is detected.
Other tests, like an ELISA assay or Polymerase Chain Reaction (PCR) to detect virus nucleic acids in serum samples, are currently being utilized to make the determination of the presence and degree of infection. However, these assays suffer from three primary defects: (1) They may not be sensitive enough to detect all HIV infected individuals, for example because some HIV infected individuals do not have detectable levels of serum antibody to HIV; (2) There may be a significant time lag between detection of HIV infection and either seroconversion or the production of significant amounts of virus circulating in the blood. In addition, some HIV infected but seronegative individuals might never convert but will remain infected throughout theirs lives. Other similar problems exist with the method for detecting HIV infection in seronegative individuals, described by Jehuda-Cohen, T. et al. (Proc. Natl. Acad. Sci. USA, 87: 3972-3076 (1990)) wherein peripheral blood mononuclear cells (PBMC) are isolated from the blood and then exposed to a mitogen such as pokeweed mitogen. In this instance incubation of isolated PBMC with pokeweed mitogen caused the PBMC to secret immunoglobulins that were specific for HIV; and lastly (3) Existing detection methods rely primarily on responses (antibody or virus levels) within the peripheral blood supply and do not detect or otherwise represent infection in the primary immune or other body organs: often these are the primary sites of HIV infection.
In sum, the failure of the ELISA, PCR and other existent assays to detect all HIV infected individuals places the population at risk by misleading HIV infected individuals with the diagnosis that they are not infected, thereby delaying the initiation of drug therapy and by making it more likely that the HIV infected individuals will unknowingly infect others. Similarly, reliance on infection assays that predict HIV presence in the peripheral blood, and not HIV infection at other primary internal infection sites within the body, may provide grossly misleading information on the whole body concentration of virus before and after drug therapy. For example, if selected drug therapies alter the shedding of virus into the blood the impact of therapy on actual virus infection may well be either overestimated or hidden by an artifactual picture of virus clearance from central reservoirs.
It is therefore evident that current methods employed for the detection of HIV-1 infection in humans, which are based on the production of HIV-1 antibodies, viral nucleic acid or gene products, do not permit direct, real-time measurement of HIV infection in vivo and thus may generate false negatives, which in turn may increases the probability of HIV infection of healthy people by infected individuals.